Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this paper we studied the effect of cyclosporin A (CyA) on interleukin 1 (IL-1) and interleukin 2 (IL-2) production and on IL-2 receptor expression by human peripheral blood lymphocytes induced to proliferate following OKT3 monoclonal antibody stimulation. CyA inhibited T-cell proliferation in a dose-dependent manner and its effect was inversely correlated with the entity of the mitogenic signal. The drug reduced not only IL-2 synthesis but also IL-1 production. CyA was also found to be able to inhibit the expression of IL-2 receptors on T cells. By supplementing with IL-1 and/or IL-2 the cultures carried out in the presence of CyA, it became evident that the inhibition of IL-2 production mainly depended on the CyA-induced reduction of IL-1 synthesis. Thus the IL-2 production by "resting" T cells had to be considered as an IL-1-dependent event. In addition it was found that the presence of IL-1 constituted a crucial requirement for the induction and the positive modulation of IL-2 receptor expression. Although IL-2 could play a role in facilitating the expression of IL-2 receptors, its effectiveness to do so depended on the presence of IL-1. In conclusion, CyA is to be considered not only as a potent immunodepressive drug but also as a valuable tool for the study of T-cell activation and proliferation.
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PMID:Inhibitory effect of cyclosporin A on the OKT3-induced peripheral blood lymphocyte proliferation. 309 Dec 67

Synovial fluid mononuclear cells (SFMC) from patients with active rheumatoid arthritis characteristically respond poorly to mitogens. In this study, mitogenic antibodies reactive with the CD3(T3) antigen on human T lymphocytes were used to analyze the basis for the deficiency. OKT3-induced proliferation and release of interleukin 1 (IL-1) and interleukin 2 (IL-2) from SFMC were depressed in all patients. Purified IL-1 or recombinant IL-2 restored proliferative responses in SFMC and increased IL-2 receptor density. Exogenous IL-1 also enhanced IL-2 release. Fractionation of SFMC supernatants on phosphocellulose columns revealed the presence of IL-1 and a potent IL-1 inhibitor. The monocyte-derived IL-1 inhibitor blocked IL-1-dependent responses of normal peripheral blood lymphocytes to OKT3, but had no effect on IL-2-dependent events. These results suggest that IL-1 inhibitor(s) in SFMC impair(s) OKT3-induced mitogenesis by interfering with the effects of IL-1 on T lymphocytes. The net result is deficient IL-2 secretion, IL-2 receptor expression, and impaired cellular proliferation. This novel inhibitory circuit provides a rational explanation for the diminished function of synovial fluid T lymphocytes in rheumatoid arthritis patients.
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PMID:Basis for defective responses of rheumatoid arthritis synovial fluid lymphocytes to anti-CD3 (T3) antibodies. 309 36

In the immune system, T-lymphocyte proliferation depends on interleukin 2 [IL-2 (T-cell growth factor)] interaction with specific receptors. In this study we show that IL-2 can specifically inhibit the proliferation of neonatal rat oligodendrocyte progenitor cells cultured in a serumless, chemically defined medium (oligodendrocyte-defined medium; ODM). IL-2 inhibited both [3H]thymidine incorporation and increase in cell number. Specificity was shown by precipitating IL-2 activity with anti-IL-2 antiserum. Furthermore, growth inhibition depended on the expression of Tac (an anti-IL-2 receptor monoclonal antibody)-positive receptors (IL-2 receptor). When cells were cultured in the presence of IL-2, both Tac-positive staining and growth inhibition were no longer expressed. The addition of interleukin 1 had no effect on [3H]thymidine incorporation or changes in cell number. However, when IL-1 was subsequently added together with IL-2, Tac expression and IL-2-mediated inhibition of cell proliferation was induced. This inhibitory effect was not due to a sensitive subpopulation because greater than 90% of the culture was Tac positive. Taken together, these data show that IL-2 can specifically inhibit oligodendrocyte proliferation and acts via Tac-positive receptors.
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PMID:Interleukin 2 mediates the inhibition of oligodendrocyte progenitor cell proliferation in vitro. 309 48

Small, resting B lymphocytes express few, if any, interleukin 2 (IL-2) receptors, but activated B cells may express such receptors. This paper examines the requirements for receptor expression. Normal murine splenocyte populations were enriched for B cells and cultured at relatively low density. IL-2 receptor expression was studied by measuring the binding of the anti-IL-2 receptor monoclonal antibody PC61. Lymphoblasts arising through stimulation by Escherichia coli lipopolysaccharide failed to express IL-2 receptors. B cells cultured with conditioned medium from concanavalin A-stimulated EL4 thymoma cells, with or without LPS, displayed IL-2 receptors. This bioactivity of EL4 conditioned medium could not be replaced by any concentration of B-cell-stimulatory factor 1 (IL-4), IL-1, IL-2, or IL-3 tested. However, the recently cloned lymphokine T-cell-replacing factor (IL-5) was a potent inducer of IL-2 receptor expression, as was the probably identical material known as eosinophil differentiation factor. The receptors so induced appeared to be functional, as receptor-expressing (but not control) lymphoblasts, responded to IL-2 by proliferation, indicative of high-affinity-receptor expression.
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PMID:T-cell-replacing factor (interleukin 5) induces expression of interleukin 2 receptors on murine splenic B cells. 311 Jul 87

The aim of this study was to examine the effect in vitro of gold sodium thiomalate (GST) on interleukin 1 (IL-1), and interleukin 2 (IL-2) production and IL-2 receptor expression in thymocytes of mice and in human peripheral blood mononuclear cells (PBMC). GST increased the proliferation of thymocytes and PBMC to suboptimal doses of T cell mitogens Con A and PHA. It induced IL-1 production of the accessory adherent cells within thymocytes and PBMC, IL-1 production in the murine macrophage line P388D1 and induced the PHA reactive thymocytes to produce IL-2 and to express IL-2 receptors. The significance of these findings is discussed.
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PMID:In vitro effects of gold sodium thiomalate on IL-1, IL-2 production, IL-2 receptor expression and IL-2 responsiveness in thymocytes and peripheral blood mononuclear cells. 311 45

We have examined the mechanisms of 1,25-dihydroxyvitamin D3 (D3)-mediated inhibition of human B cell differentiation to immunoglobulin (Ig) secreting cells. B lymphocytes were purified from human tonsils and peripheral blood mononuclear cells. Mononuclear cells were separated into adherent cells and nonadherent cells. Cells were stimulated with Staphylococcus aureus Cowen I (SAC) or pokeweed mitogen (PWM) for 7 days and immunoglobulin production was measured by ELISA assay, 1,25-dihydroxyvitamin D3 was added at different times during cultures. 1,25-Dihydroxyvitamin D3, in a dose-dependent manner, inhibited both SAC and PWM-induced Ig production by mononuclear cells. The maximum inhibition was observed when 1,25-dihydroxyvitamin D3 was added at the beginning of culture, but inhibition could still be observed when 1,25-dihydroxyvitamin D3 was added on day 4 of cultures. The inhibitory effect of 1,25-dihydroxyvitamin D3 on Ig production was significantly greater on mononuclear cells than on nonadherent cells. Addition of in vitro purified IL-1 to nonadherent cells enhanced 1,25-dihydroxyvitamin D3-induced inhibition of Ig production. 1,25-Dihydroxyvitamin D3 also inhibited the expression of IL-2 receptors on B cells activated with SAC. 1,25-dihydroxyvitamin D3 did not inhibit Ig production by SAC preactivated B cell blasts in response to T cell supernatants. These data suggest that vitamin D3 inhibits Ig production by inhibiting IL-2 receptor expression on B cells and via its effect on adherent macrophages. Vitamin D3 does not influence the effect of differentiation factors on activated B cells that have already expressed growth/differentiation factor receptors.
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PMID:1,25-Dihydroxyvitamin D3-mediated inhibition of human B cell differentiation. 311 62

The thymocyte costimulator (LAF) assay, the standard biological test used for IL-1 titration, has a low sensitivity and lacks specificity since it can be potentiated by the IL-2 which is frequently present in IL-1-containing biological fluids. We describe here a new IL-1 titration method which takes advantage of the capacity of a thymoma line, EL4-6.1, to differentiate and express IL-2 receptors upon stimulation by IL-1 in the presence of a suboptimal dose of phorbol diester. Membrane IL-2R measurement on this indicator cell line permits the detection of 1-2 X 10(-4) ng/ml IL-1, compared to 5 X 10(-2) ng/ml in the LAF assay. In addition, rIL-2 up to 250 U/ml has no effect on IL-1 measurement by this assay, which also exhibits a 100-fold lower sensitivity to inhibitory effects of prostaglandin, compared to the LAF assay. Finally, tumor necrosis factor alpha only exerts a weak costimulation effect at very high doses. A flow cytometry technique and an ELISA are described for IL-2 receptor detection. Due to its high sensitivity and specificity, this novel assay should now permit reliable IL-1 titration in biological fluids such as IL-2-rich lymphocyte culture supernatants.
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PMID:A sensitive, IL-2-independent, assay for IL-1. 312 57

Cell sorter-purified small splenic L3T4+ cells from B6 mice were clonally expanded under limiting dilution (LD) conditions by coculture for 4-6 days with irradiated allogeneic stimulator cells in culture medium supplemented with various growth factor preparations. Proliferating L3T4+ cell clones were detected by [3H]thymidine uptake; interleukin 2 (IL-2) production of restimulated L3T4+ cell clones was measured in a sensitive colorimetric assay. IL-3 (but not IL-1 or IL-4) supported clonal expansion in vitro of many L3T4+ cell clones produced IL-2. The data were consistent with the hypothesis that only a single titrated precursor cell was limiting in the system. In the response to class II (bm12) H-2 alloantigen, 1 in 40-200 L3T4+ cells was induced to clonal growth; in the response to class I (bm1) H-2 alloantigen, a tenfold lower frequency (1 in 600-800) of inducible L3T4+ B6 cells was measured. A fraction of the generated L3T4+ cell clones showed IL-2-independent growth: anti-IL-2 receptor monoclonal antibodies (MoAb) (7D4 and PC61.5) blocked the proliferation of about 80% of the IL-2-producing L3T4+ cell clones, while about 20% of these clones seemed resistant to inhibition of proliferation by these MoAb. We have thus defined an LD system with high cloning efficiency for L3T4+ cells that does not depend on exogenous IL-2 supplements.
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PMID:Limiting dilution analysis of the response of murine L3T4+ spleen cells to alloantigen. 312 76

Monoclonal T cell colonies can be grown in agar culture from quiescent T lymphocytes under PHA stimulation, provided that (1) a low number of T lymphocytes (less than or equal to 5 X 10(4)/ml) is seeded, (2) IL-2 is added to the culture, and (3) a high number of accessory B cells (greater than or equal to 5 X 10(5)/ml) is present in contact with the T lymphocytes. Under these culture conditions the colony progenitors can be ascribed to the CD4 subset, whereas CD8 lymphocytes do not generate colonies. This finding is surprising since both CD4 and CD8 lymphocytes may be cloned in liquid culture. We now report the appropriate conditions required to grow cytotoxic CD8 lymphocyte colonies in agar. CD8 colony growth is dependent upon IL-2-IL-2 receptor interaction and is inhibited by anti-IL-2 receptor antibodies. In addition to PHA, accessory B cells and IL-2, an additional signal provided by recombinant IL-1 is necessary for CD8 colony formation. Exogenous IL-1 can be replaced by irradiated CD4 lymphocytes which stimulate the expression of membrane IL-1 activity in the accessory B cells. In addition, colony growth from quiescent but not preactivated CD8 lymphocytes is inhibited by anti-IL-1 antibodies. Altogether, the data show that an IL-1 signal is required for the induction of IL-2 responsive IL-2 receptors on quiescent CD8 colony forming cells.
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PMID:Activation by PHA of CD8 lymphocytes into clonal colony forming cells. Role of interleukin-1. 313 8

In the model system used here, cross-linking of T-cell receptor structures (TCR) by antigen-presenting cells (APCs) is substituted by the use of anti-F23.1 anti-T-cell receptor monoclonal antibody immobilized on Sepharose beads. We show that CR cross-linking of resting murine CD8+ T cells seeded at low cell densities is insufficient to induce responsiveness to the growth-promoting effect of interleukin-2 (IL-2), i.e. fails to induce expression of functional IL-2 receptors. The macrophage cell-line product, IL-2 receptor-inducing factor (RIF), but not IL-1, IL-3, IL-4 and interferon-gamma (IFN-gamma) functions efficiently as a co-stimulator. Once activated, growth of CD8+ T cells is driven entirely by IL-2. We conclude that two restriction points control the activation of resting CD8+ T cells. While cross-linking of TCR is essential as the first step, RIF is required as the competence factor to induce IL-2 responsiveness. We consider the possibility that the ability of APCs to produce RIF determines the immunogenicity of APCs towards antigen-reactive resting CD8+ T cells.
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PMID:Two distinct signals regulate induction of IL-2 responsiveness in CD8+ murine T cells. 313 55


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